Lymphoblastic Leukemia, AcutePhase 1NCT00995137
Genetically Modified Haploidentical Natural Killer Cell Infusions for B-Lineage Acute Lymphoblastic Leukemia
A Phase 1 study testing NK Cell Infusion in people with Lymphoblastic Leukemia, Acute, run by St. Jude Children's Research Hospital at 1 site in United States.
Trial summary
This study will determine the maximum tolerated dose of genetically modified natural killer (NK) cells in research participants with relapsed or refractory B-lineage acute lymphoblastic leukemia (ALL). Read more about this study
- Who is it for?
- Ages Up to 18 years
- Conditions the study is for
- Lymphoblastic Leukemia, Acute
- What is being tested?
- NK Cell Infusion
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 14 participants
- Where
- 1 siteUnited States
- Study dates
- Oct 2009to May 2014
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Up to 18 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Age: less than or equal to 18 years of age. May be greater than 18 years of age if currently a St. Jude patient.
- Patients with relapsed or refractory B-lineage ALL who are not eligible for hematopoietic stem cell transplantation (HSCT) because their leukemia is not in remission (>5% blasts in bone marrow as evidenced either by morphology or by flow cytometry).
- Shortening fraction greater than or equal to 25%.
- Glomerular filtration rate greater than or equal to 50 cc/min/1.73 m2.
- Pulse oximetry greater than or equal to 92% on room air.
- Direct bilirubin less than or equal to 3.0 mg/dL.
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- Alanine aminotransferase (ALT) is no more than 2 times the upper limit of normal.
- Aspartate transaminases (AST) is no more than 2 times the upper limit of normal.
- Karnofsky or Lansky performance score of greater than or equal to 50.
- No known allergy to murine products or HAMA testing results within normal limits.
- No prior receipt of a gene-transfer agent (e.g. retroviral, adenoviral, lentiviral vector).
- Does not have a current pleural or pericardial effusion.
- Has a suitable adult family member donor available for NK cell donation.
- Has recovered from all acute NCI Common Toxicity Criteria grade II-IV non-hematologic acute toxicities resulting from previous therapy as per the judgment of the principal investigator.
- At least two weeks since receipt of any biological therapy, systemic chemotherapy, and/or radiation therapy.
- Is not receiving more than the equivalent of prednisone 10 mg daily.
Who cannot join
- Pregnant (negative serum or urine pregnancy test to be conducted within 7 days prior to enrollment)
- Breastfeeding
Trial locations and contacts
1 site in 1 country.
United States1 site
St Jude Children's Research Hospital
Memphis, Tennessee, 38105-3678
About this study
Official title: Pilot Study of Genetically Modified Haploidentical Natural Killer Cell Infusions for B-Lineage Acute Lymphoblastic Leukemia
This study will determine the maximum tolerated dose of genetically modified natural killer (NK) cells in research participants with relapsed or refractory B-lineage acute lymphoblastic leukemia (ALL).
Read the detailed description
NK cell cytotoxicity is most powerful against acute myeloid leukemia (AML) cells, whereas their capacity to lyse ALL cells is generally low and difficult to predict. A novel method has been developed to redirect NK cells towards CD19, a molecule highly expressed on the surface of B-lineage ALL cells, but not expressed on normal cells other than B-lymphocytes. In this method, donor NK cells are first expanded by co-culture with irradiated K562 cell line modified to express membrane bound IL-15 and 41BB ligand (K562-mb15-41BBL). Overexpansion of these proteins promotes selective growth of NK cells. Then, the expanded NK cells are transduced with a signaling receptor that binds to CD19 (anti-CD19-BB-zeta). NK cells expressing these receptors showed powerful anti-leukemic activity against CD19+ ALL cells in vitro and in an animal model of leukemia.
This study represents the translation of laboratory findings into clinical application. It will allow us to assess the safety of infusing genetically modified NK cells into research participants who have chemotherapy refractory or relapse B-lineage ALL. In this same cohort, we also intend to study the in vivo lifespan and phenotype of genetically modified NK cells and explore the efficacy of NK cells in patients with B-lineage ALL.
- Conditions
- Lymphoblastic Leukemia, Acute
- Being tested
- NK Cell Infusion
- Keywords
- Relapsed or refractory B-Lineage ALL
- Medical subject headings
- Precursor Cell Lymphoblastic Leukemia-Lymphoma, Recurrence
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NK Cell InfusionBiological
Infusing genetically modified NK cells into research participants who have chemotherapy refractory or relapse B-lineage ALL.
| Study group | Role | What they receive |
|---|---|---|
| relapse B-Lineage ALL | Experimental | All patients meeting the eligibility criteria.
Intervention: NK Cell Infusion Receives: Biological: NK Cell Infusion |
What is being measured
The primary outcome is the main question the study is designed to answer.
This study will determine the maximum tolerated dose of genetically modified NK cells in research participants with relapsed or refractory B-lineage ALL
Measured: 30 days after the enrollment of the last patient
Secondary outcomes (2)
This study will determine the persistence and phenotype of genetically modified NK cells in research participants with relapsed or refractory B-lineage ALL.
Measured: 30 days after the enrollment of the last patient
This study will explore the efficacy of genetically modified NK cells in research participants with relapsed or refractory B-lineage ALL.
Measured: 30 days after the enrollment of the last patient
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Oct 2009 (estimated)
- Study startOct 2009
- Primary completionMay 2013
- Study completionMay 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Lymphoblastic Leukemia, AcuteStudies of the same condition, open and under way.
- More trials run by St. Jude Children's Research HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 14 participants (actual)
Sponsor and investigators
- Lead sponsor
- St. Jude Children's Research Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI), Assisi Foundation
- Responsible party
- Sponsor
- Investigators
- David Shook, MD, Principal investigator, St. Jude Children's Research Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00995137
- Sponsor's protocol ID
- NKCD19
- Other IDs
- R01CA113482, NCI-2011-01226
- Status last verified
- Feb 2015
- First submitted
- 14 Oct 2009
- Last updated
- 26 Apr 2017
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Del Zotto G, Marcenaro E, Vacca P, Sivori S, Pende D, Della Chiesa M, Moretta F, Ingegnere T, Mingari MC, Moretta A, Moretta L. Markers and function of human NK cells in normal and pathological conditions. Cytometry B Clin Cytom. 2017 Mar;92(2):100-114. doi: 10.1002/cyto.b.21508. Epub 2017 Feb 12.
PubMed 28054442
Study at a glance
From the registry record, last updated by the sponsor on 26 Apr 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pilot Study of Genetically Modified Haploidentical Natural Killer Cell Infusions for B-Lineage Acute Lymphoblastic Leukemia
- ClinicalTrials.gov ID
- NCT00995137
- Acronym / sponsor ID
- NKCD19
- Conditions
- Lymphoblastic Leukemia, Acute
- Keywords
- Relapsed or refractory B-Lineage ALL
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 14 participants (actual)
- Lead sponsor
- St. Jude Children's Research HospitalUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI), Assisi Foundation
- Study start
- Oct 2009
- Primary completion
- May 2013 (actual)
- Study completion
- May 2014 (actual)
- First posted
- 15 Oct 2009 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study will determine the maximum tolerated dose of genetically modified natural killer (NK) cells in research participants with relapsed or refractory B-lineage acute lymphoblastic leukemia (ALL).
Detailed description
NK cell cytotoxicity is most powerful against acute myeloid leukemia (AML) cells, whereas their capacity to lyse ALL cells is generally low and difficult to predict. A novel method has been developed to redirect NK cells towards CD19, a molecule highly expressed on the surface of B-lineage ALL cells, but not expressed on normal cells other than B-lymphocytes. In this method, donor NK cells are first expanded by co-culture with irradiated K562 cell line modified to express membrane bound IL-15 and 41BB ligand (K562-mb15-41BBL). Overexpansion of these proteins promotes selective growth of NK cells. Then, the expanded NK cells are transduced with a signaling receptor that binds to CD19 (anti-CD19-BB-zeta). NK cells expressing these receptors showed powerful anti-leukemic activity against CD19+ ALL cells in vitro and in an animal model of leukemia.
This study represents the translation of laboratory findings into clinical application. It will allow us to assess the safety of infusing genetically modified NK cells into research participants who have chemotherapy refractory or relapse B-lineage ALL. In this same cohort, we also intend to study the in vivo lifespan and phenotype of genetically modified NK cells and explore the efficacy of NK cells in patients with B-lineage ALL.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| relapse B-Lineage ALL | Experimental | Biological: NK Cell InfusionAll patients meeting the eligibility criteria. Intervention: NK Cell Infusion |
Who may qualify
- Ages
- Up to 18 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (16 listed)
- Age: less than or equal to 18 years of age. May be greater than 18 years of age if currently a St. Jude patient.
- Patients with relapsed or refractory B-lineage ALL who are not eligible for hematopoietic stem cell transplantation (HSCT) because their leukemia is not in remission (>5% blasts in bone marrow as evidenced either by morphology or by flow cytometry).
- Shortening fraction greater than or equal to 25%.
- Glomerular filtration rate greater than or equal to 50 cc/min/1.73 m2.
- Pulse oximetry greater than or equal to 92% on room air.
Key exclusion criteria (2 listed)
- Pregnant (negative serum or urine pregnancy test to be conducted within 7 days prior to enrollment)
- Breastfeeding
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| NK Cell InfusionInfusing genetically modified NK cells into research participants who have chemotherapy refractory or relapse B-lineage ALL. | Biological | relapse B-Lineage ALL |
Primary outcome
This study will determine the maximum tolerated dose of genetically modified NK cells in research participants with relapsed or refractory B-lineage ALL
Time frame: 30 days after the enrollment of the last patient
2 secondary outcomes
This study will determine the persistence and phenotype of genetically modified NK cells in research participants with relapsed or refractory B-lineage ALL.
Time frame: 30 days after the enrollment of the last patient
This study will explore the efficacy of genetically modified NK cells in research participants with relapsed or refractory B-lineage ALL.
Time frame: 30 days after the enrollment of the last patient
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Apr 2017.
- Derived from this study: PubMed 28054442Del Zotto G, Marcenaro E, Vacca P, Sivori S, Pende D, Della Chiesa M, Moretta F, Ingegnere T, Mingari MC, Moretta A, Moretta L. Markers and function of human NK cells in normal and pathological conditions. Cytometry B Clin Cytom. 2017 Mar;92(2):100-114. doi: 10.1002/cyto.b.21508. Epub 2017 Feb 12.
- St. Jude Children's Research HospitalLink provided by the sponsor.
- Clinical Trials Open at St. JudeLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
David Shook, MD principal investigator
St. Jude Children's Research Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing NK Cell Infusion in people with Lymphoblastic Leukemia, Acute, run by St. Jude Children's Research Hospital at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 16 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 26 Apr 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
This study will determine the maximum tolerated dose of genetically modified NK cells in research participants with relapsed or refractory B-lineage ALL (time frame: 30 days after the enrollment of the last patient). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00995137, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Apr 2017.